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References

Trials

Economics

Properties

Spectra

Taxonomy

Felodipine

Targets (13)Enzymes (6)Transporters (2)Biointeractions (19)

Identification

Name

Felodipine

Accession Number

DB01023 (APRD00374)

Type

Small Molecule

Groups

Approved, Investigational

Description

Felodipine is a long-acting 1,4-dihydropyridine calcium channel blocker (CCB)b. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, felodipine prevents calcium-dependent myocyte contraction and vasoconstriction. Felodipine is the most potent CCB in use and is unique in that it exhibits fluorescent activity. In addition to binding to L-type calcium channels, felodipine binds to a number of calcium-binding proteins, exhibits competitive antagonism of the mineralcorticoid receptor, inhibits the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase, and blocks calcium influx through voltage-gated T-type calcium channels. Felodipine is used to treat mild to moderate essential hypertension.

Structure

Similar Structures

Synonyms

(±)-ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate
3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate
4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid ethyl methyl ester
Felodipina
Felodipine
Felodipinum

Product Images

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Felodipine	Tablet, extended release	10 mg/1	Oral	Med Pharma Co., Ltd.	2011-06-07	2012-05-15
Felodipine	Tablet, extended release	5 mg/1	Oral	Med Pharma Co., Ltd.	2011-06-07	2012-05-15
Felodipine	Tablet, extended release	2.5 mg/1	Oral	Med Pharma Co., Ltd.	2011-06-07	2012-05-15
Felodipineextended-release Tablets	Tablet, extended release	10 mg/1	Oral	Ranbaxy Inc.	2008-09-10	Not applicable
Felodipineextended-release Tablets	Tablet, extended release	5 mg/1	Oral	Ranbaxy Inc.	2008-09-10	Not applicable
Felodipineextended-release Tablets	Tablet, extended release	2.5 mg/1	Oral	Ranbaxy Inc.	2008-09-10	Not applicable
Plendil	Tablet, extended release	10 mg/1	Oral	Astra Zeneca Lp	1991-09-16	2011-12-31
Plendil	Tablet, extended release	10 mg/1	Oral	Physicians Total Care, Inc.	1991-07-25	2011-05-31
Plendil	Tablet, extended release	5 mg/1	Oral	Astra Zeneca Lp	1991-09-16	2012-01-31
Plendil	Tablet, extended release	5 mg/1	Oral	Physicians Total Care, Inc.	1991-07-25	2011-05-31

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Apo-felodipine	Tablet, extended release	2.5 mg	Oral	Apotex Corporation	2016-04-22	Not applicable
Apo-felodipine	Tablet, extended release	10 mg	Oral	Apotex Corporation	2016-04-22	Not applicable
Apo-felodipine	Tablet, extended release	5 mg	Oral	Apotex Corporation	2016-04-22	Not applicable
Felodipine	Tablet, film coated	2.5 mg/1	Oral	Physicians Total Care, Inc.	2005-11-08	Not applicable
Felodipine	Tablet, film coated, extended release	10 mg/1	Oral	Mylan Pharmaceuticals	2008-04-18	Not applicable
Felodipine	Tablet, film coated, extended release	10 mg/1	Oral	Wockhardt	2010-12-05	Not applicable
Felodipine	Tablet, extended release	10 mg/1	Oral	Torrent Pharmaceuticals Limited	2011-11-28	Not applicable
Felodipine	Tablet, extended release	5 mg/1	Oral	Heritage	2013-11-08	Not applicable
Felodipine	Tablet, film coated, extended release	5 mg/1	Oral	Jubilant Cadista Pharmaceuticals Inc.	2016-08-19	Not applicable
Felodipine	Tablet, extended release	10 mg/1	Oral	A-S Medication Solutions	2011-11-28	2016-04-30

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Altace Plus Felodipine 2.5mg + 2.5mg	Felodipine (2.5 mg) + Ramipril (2.5 mg)	Tablet	Oral	Sanofi Aventis	2006-06-27	2012-10-10
Altace Plus Felodipine 5mg + 5mg	Felodipine (5 mg) + Ramipril (5 mg)	Tablet	Oral	Sanofi Aventis	2006-06-27	2012-10-15
Lexxel	Felodipine (5 mg/1) + Enalapril maleate (5 mg/1)	Tablet, extended release	Oral	Astra Zeneca Lp	1996-12-27	2010-08-31

International/Other Brands

Felodur ER / Felogard / Penedil / Plendil Depottab (AstraZeneca) / Plendil ER (AstraZeneca) / Plendil Retard (AstraZeneca) / Splendil

Categories

UNII

OL961R6O2C

CAS number

72509-76-3

Weight

Average: 384.254
Monoisotopic: 383.069113515

Chemical Formula

C₁₈H₁₉Cl₂NO₄

InChI Key

RZTAMFZIAATZDJ-UHFFFAOYSA-N

InChI

InChI=1S/C18H19Cl2NO4/c1-5-25-18(23)14-10(3)21-9(2)13(17(22)24-4)15(14)11-7-6-8-12(19)16(11)20/h6-8,15,21H,5H2,1-4H3

IUPAC Name

3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

SMILES

CCOC(=O)C1=C(C)NC(C)=C(C1C1=C(Cl)C(Cl)=CC=C1)C(=O)OC

Pharmacology

Indication

For the treatment of mild to moderate essential hypertension.

Associated Conditions

High Blood Pressure (Hypertension)

Pharmacodynamics

Felodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction; however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. The pharmacologic significance of T-type calcium channel blockade is unknown. Felodipine also binds to calmodulin and inhibits calmodulin-dependent calcium release from the sarcoplasmic reticulum. The effect of this interaction appears to be minor. Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. Felodipine also acts as an antagonist to the mineralcorticoid receptor by competing with aldosterone for binding and blocking aldosterone-induced coactivator recruitment of the mineralcorticoid receptor. Felodipine is able to bind to skeletal and cardiac muscle isoforms of troponin C, one of the key regulatory proteins in muscle contraction. Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. Similar to other DHP CCBs, felodipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives felodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, felodipine has little effect on cardiac myocytes and conduction cells.

Mechanism of action

Felodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. It reversibly competes against nitrendipine and other DHP CCBs for DHP binding sites in vascular smooth muscle and cultured rabbit atrial cells. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of felodipine result in an overall decrease in blood pressure. Felodipine may be used to treat mild to moderate essential hypertension.

Target	Actions	Organism
AVoltage-dependent L-type calcium channel subunit alpha-1C	inhibitor	Human
AVoltage-dependent calcium channel subunit alpha-2/delta-1	inhibitor	Human
AVoltage-dependent L-type calcium channel subunit beta-2	inhibitor	Human
AVoltage-dependent L-type calcium channel subunit alpha-1D	inhibitor	Human
AVoltage-dependent L-type calcium channel subunit alpha-1S	inhibitor	Human
UVoltage-dependent T-type calcium channel subunit alpha-1H	inhibitor	Human
UVoltage-dependent calcium channel subunit alpha-2/delta-2	inhibitor	Human
UCalmodulin	other	Human
UCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B	inhibitor	Human
UCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A	inhibitor	Human
UMineralocorticoid receptor	antagonist	Human
UTroponin C, skeletal muscle	other	Human
UTroponin C, slow skeletal and cardiac muscles	other	Human

Absorption

Is completely absorbed from the gastrointestinal tract; however, extensive first-pass metabolism through the portal circulation results in a low systemic availability of 15%. Bioavailability is unaffected by food.

Volume of distribution

10 L/kg

Protein binding

99%, primarily to the albumin fraction.

Metabolism

Hepatic metabolism primarily via cytochrome P450 3A4. Six metabolites with no appreciable vasodilatory effects have been identified.

Felodipine
dehydrofelodipine

Route of elimination

Although higher concentrations of the metabolites are present in the plasma due to decreased urinary excretion, these are inactive. Animal studies have demonstrated that felodipine crosses the blood-brain barrier and the placenta.

Half life

17.5-31.5 hours in hypertensive patients; 19.1-35.9 hours in elderly hypertensive patients; 8.5-19.7 in healthy volunteers.

Clearance

0.8 L/min [Young healthy subjects]

Toxicity

Symptoms of overdose include excessive peripheral vasodilation with marked hypotension and possibly bradycardia. Oral rat LD₅₀ is 1050 mg/kg.

Affected organisms

Humans and other mammals

Pathways

Pathway	Category
Felodipine Metabolism Pathway	Drug metabolism
Felodipine Action Pathway	Drug action

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
(R)-warfarin	The metabolism of (R)-warfarin can be decreased when combined with Felodipine.
(S)-Warfarin	The metabolism of (S)-Warfarin can be decreased when combined with Felodipine.
Abafungin	The therapeutic efficacy of Abafungin can be increased when used in combination with Felodipine.
Abemaciclib	The serum concentration of Abemaciclib can be increased when it is combined with Felodipine.
Acebutolol	The serum concentration of Acebutolol can be increased when it is combined with Felodipine.
Aceclofenac	The therapeutic efficacy of Felodipine can be decreased when used in combination with Aceclofenac.
Acemetacin	The therapeutic efficacy of Felodipine can be decreased when used in combination with Acemetacin.
Acepromazine	The risk or severity of hypotension can be increased when Acepromazine is combined with Felodipine.
Acetazolamide	The metabolism of Felodipine can be decreased when combined with Acetazolamide.
Acetylsalicylic acid	Felodipine may increase the anticoagulant activities of Acetylsalicylic acid.

Food Interactions

Grapefruit down regulates post-translational expression of CYP3A4, the major metabolizing enzyme of nifedipine. Grapefruit, in all forms (e.g. whole fruit, juice and rind), can significantly increase serum levels of nifedipine and may cause toxicity. Avoid grapefruit products while on this medication.
Take without regard to meals.

References

Synthesis Reference

Vinay Sharma, "Preparation of micron-size felodipine particles by microfluidization." U.S. Patent US20020086061, issued July 04, 2002.

US20020086061

General References

Dunselman PH, Edgar B: Felodipine clinical pharmacokinetics. Clin Pharmacokinet. 1991 Dec;21(6):418-30. [PubMed:1782737]

External Links

Human Metabolome Database: HMDB0015158
KEGG Drug: D00319
PubChem Compound: 3333
PubChem Substance: 46506968
ChemSpider: 3216
BindingDB: 189379
ChEBI: 585948
ChEMBL: CHEMBL1480
Therapeutic Targets Database: DAP000487
PharmGKB: PA449591
IUPHAR: 4190
Guide to Pharmacology: GtP Drug Page
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
PDRhealth: PDRhealth Drug Page
Wikipedia: Felodipine

ATC Codes

C08CA02 — Felodipine

C09BB05 — Ramipril and felodipine

AHFS Codes

24:28.08 — Dihydropyridines

FDA label

Download (228 KB)

MSDS

Download (55.4 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Healthy Volunteers	1
1	Completed	Treatment	Food-Drug Interactions	1
3	Completed	Prevention	Atherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension) / High Cholesterol / Type 2 Diabetes Mellitus	1
3	Completed	Treatment	BMI >30 kg/m2 / High Blood Pressure (Hypertension)	1
4	Completed	Prevention	Disorders Related to Lung Transplantation	1
4	Completed	Treatment	High Blood Pressure (Hypertension)	2
4	Completed	Treatment	High Blood Pressure (Hypertension) / Left Ventricular Hypertrophy	1
4	Unknown Status	Treatment	High Blood Pressure (Hypertension) / Sexual Dysfunctions	1
Not Available	Completed	Not Available	Healthy Volunteers	2
Not Available	Completed	Not Available	High Blood Pressure (Hypertension)	1
Not Available	Completed	Treatment	High Blood Pressure (Hypertension)	1
Not Available	Unknown Status	Basic Science	High Blood Pressure (Hypertension) / Insulin Resistance / Microcirculation	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

A-S Medication Solutions LLC
AstraZeneca Inc.
Atlantic Biologicals Corporation
Bryant Ranch Prepack
Cardinal Health
Heartland Repack Services LLC
Lake Erie Medical and Surgical Supply
Liberty Pharmaceuticals
Merck & Co.
Murfreesboro Pharmaceutical Nursing Supply
Mutual Pharmaceutical Co.
Mylan
Nucare Pharmaceuticals Inc.
PD-Rx Pharmaceuticals Inc.
Physicians Total Care Inc.
Preferred Pharmaceuticals Inc.
Prepackage Specialists
Prepak Systems Inc.
Prescript Pharmaceuticals
Ranbaxy Laboratories
Resource Optimization and Innovation LLC
Richmond Pharmacy
Sandhills Packaging Inc.
UDL Laboratories
Va Cmop Dallas
Vangard Labs Inc.

Dosage forms

Form	Route	Strength
Tablet	Oral
Tablet, film coated	Oral	2.5 mg/1
Tablet, film coated, extended release	Oral	10 mg/1
Tablet, film coated, extended release	Oral	2.5 mg/1
Tablet, film coated, extended release	Oral	5 mg/1
Tablet, extended release	Oral	10 mg/1
Tablet, extended release	Oral	2.5 mg/1
Tablet, extended release	Oral	5 mg/1
Tablet, extended release	Oral
Tablet, extended release	Oral	10 mg
Tablet, extended release	Oral	2.5 mg
Tablet, extended release	Oral	5 mg

Prices

Unit description	Cost	Unit
Plendil 10 mg 24 Hour tablet	3.17USD	tablet
Plendil er 10 mg tablet	3.05USD	tablet
Plendil 10 mg tablet sa	2.96USD	tablet
Felodipine 10 mg 24 Hour tablet	2.95USD	tablet
Plendil er 2.5 mg tablet	2.94USD	tablet
Felodipine er 10 mg tablet	2.72USD	tablet
Plendil er 5 mg tablet	2.6USD	tablet
Plendil 5 mg 24 Hour tablet	1.77USD	tablet
Plendil 2.5 mg 24 Hour tablet	1.76USD	tablet
Felodipine 5 mg 24 Hour tablet	1.67USD	tablet
Plendil 2.5 mg tablet sa	1.65USD	tablet
Plendil 5 mg tablet sa	1.65USD	tablet
Felodipine 2.5 mg 24 Hour tablet	1.57USD	tablet
Felodipine er 2.5 mg tablet	1.51USD	tablet
Felodipine er 5 mg tablet	1.51USD	tablet
Renedil 10 mg Extended-Release Tablet	1.22USD	tablet
Plendil 10 mg Extended-Release Tablet	1.15USD	tablet
Renedil 5 mg Extended-Release Tablet	0.81USD	tablet
Plendil 5 mg Extended-Release Tablet	0.77USD	tablet
Sandoz Felodipine 10 mg Extended-Release Tablet	0.73USD	tablet
Renedil 2.5 mg Extended-Release Tablet	0.6USD	tablet
Plendil 2.5 mg Extended-Release Tablet	0.57USD	tablet
Sandoz Felodipine 5 mg Extended-Release Tablet	0.48USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	145 °C	Not Available
water solubility	19.7 mg/L	Not Available
logP	3.86	SANGSTER (1994)
Caco2 permeability	-4.64	ADME Research, USCD

Predicted Properties

Property	Value	Source
Water Solubility	0.00715 mg/mL	ALOGPS
logP	4.36	ALOGPS
logP	3.44	ChemAxon
logS	-4.7	ALOGPS
pKa (Strongest Acidic)	19.46	ChemAxon
pKa (Strongest Basic)	-6.6	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	64.63 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	99.2 m³·mol^-1	ChemAxon
Polarizability	37.96 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.9878
Blood Brain Barrier	-	0.83
Caco-2 permeable	+	0.8867
P-glycoprotein substrate	Substrate	0.5149
P-glycoprotein inhibitor I	Inhibitor	0.8563
P-glycoprotein inhibitor II	Non-inhibitor	0.8383
Renal organic cation transporter	Non-inhibitor	0.8664
CYP450 2C9 substrate	Non-substrate	0.8357
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Substrate	0.6954
CYP450 1A2 substrate	Inhibitor	0.9106
CYP450 2C9 inhibitor	Inhibitor	0.8948
CYP450 2D6 inhibitor	Non-inhibitor	0.9232
CYP450 2C19 inhibitor	Inhibitor	0.8994
CYP450 3A4 inhibitor	Inhibitor	0.7959
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.9304
Ames test	Non AMES toxic	0.7849
Carcinogenicity	Non-carcinogens	0.7511
Biodegradation	Not ready biodegradable	0.9527
Rat acute toxicity	2.4526 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9455
hERG inhibition (predictor II)	Non-inhibitor	0.8734

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	Not Available
MS/MS Spectrum - , positive	LC-MS/MS	splash10-0udu-0139000000-085071c20c5d0c134d8f

Taxonomy

Description: This compound belongs to the class of organic compounds known as dihydropyridinecarboxylic acids and derivatives. These are compounds containing a dihydropyridine moiety bearing a carboxylic acid group.
Kingdom: Organic compounds
Super Class: Organoheterocyclic compounds
Class: Pyridines and derivatives
Sub Class: Hydropyridines
Direct Parent: Dihydropyridinecarboxylic acids and derivatives
Alternative Parents: Dichlorobenzenes / Dicarboxylic acids and derivatives / Aryl chlorides / Vinylogous amides / Methyl esters / Enoate esters / Amino acids and derivatives / Enamines / Dialkylamines / Azacyclic compounds
show 5 more
Substituents: Dihydropyridinecarboxylic acid derivative / 1,2-dichlorobenzene / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Dicarboxylic acid or derivatives / Benzenoid / Vinylogous amide
show 22 more
Molecular Framework: Aromatic heteromonocyclic compounds
External Descriptors: ethyl ester, dichlorobenzene, methyl ester, dihydropyridine (CHEBI:585948)

Targets

Details1. Voltage-dependent L-type calcium channel subunit alpha-1C

Kind: Protein
Organism: Human
Pharmacological action: Yes
Actions: Inhibitor

General Function: Voltage-gated calcium channel activity
Specific Function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name: CACNA1C
Uniprot ID: Q13936
Uniprot Name: Voltage-dependent L-type calcium channel subunit alpha-1C
Molecular Weight: 248974.1 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [PubMed:10525060]
Zahradnikova A, Minarovic I, Zahradnik I: Competitive and cooperative effects of Bay K8644 on the L-type calcium channel current inhibition by calcium channel antagonists. J Pharmacol Exp Ther. 2007 Aug;322(2):638-45. Epub 2007 May 2. [PubMed:17475903]
Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]

Details2. Voltage-dependent calcium channel subunit alpha-2/delta-1

Kind: Protein
Organism: Human
Pharmacological action: Yes
Actions: Inhibitor

General Function: Voltage-gated calcium channel activity
Specific Function: The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-...
Gene Name: CACNA2D1
Uniprot ID: P54289
Uniprot Name: Voltage-dependent calcium channel subunit alpha-2/delta-1
Molecular Weight: 124566.93 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [PubMed:10525060]
Zahradnikova A, Minarovic I, Zahradnik I: Competitive and cooperative effects of Bay K8644 on the L-type calcium channel current inhibition by calcium channel antagonists. J Pharmacol Exp Ther. 2007 Aug;322(2):638-45. Epub 2007 May 2. [PubMed:17475903]
Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]

Details3. Voltage-dependent L-type calcium channel subunit beta-2

Kind: Protein
Organism: Human
Pharmacological action: Yes
Actions: Inhibitor

General Function: Voltage-gated calcium channel activity
Specific Function: The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and ina...
Gene Name: CACNB2
Uniprot ID: Q08289
Uniprot Name: Voltage-dependent L-type calcium channel subunit beta-2
Molecular Weight: 73579.925 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [PubMed:10525060]
Zahradnikova A, Minarovic I, Zahradnik I: Competitive and cooperative effects of Bay K8644 on the L-type calcium channel current inhibition by calcium channel antagonists. J Pharmacol Exp Ther. 2007 Aug;322(2):638-45. Epub 2007 May 2. [PubMed:17475903]
Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]

Details4. Voltage-dependent L-type calcium channel subunit alpha-1D

Kind: Protein
Organism: Human
Pharmacological action: Yes
Actions: Inhibitor

General Function: Voltage-gated calcium channel activity involved sa node cell action potential
Specific Function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name: CACNA1D
Uniprot ID: Q01668
Uniprot Name: Voltage-dependent L-type calcium channel subunit alpha-1D
Molecular Weight: 245138.75 Da

References

Sinnegger-Brauns MJ, Huber IG, Koschak A, Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J: Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol. 2009 Feb;75(2):407-14. doi: 10.1124/mol.108.049981. Epub 2008 Nov 24. [PubMed:19029287]

Details5. Voltage-dependent L-type calcium channel subunit alpha-1S

Kind: Protein
Organism: Human
Pharmacological action: Yes
Actions: Inhibitor

General Function: Voltage-gated calcium channel activity
Specific Function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name: CACNA1S
Uniprot ID: Q13698
Uniprot Name: Voltage-dependent L-type calcium channel subunit alpha-1S
Molecular Weight: 212348.1 Da

References

Peterson BZ, Catterall WA: Allosteric interactions required for high-affinity binding of dihydropyridine antagonists to Ca(V)1.1 Channels are modulated by calcium in the pore. Mol Pharmacol. 2006 Aug;70(2):667-75. Epub 2006 May 4. [PubMed:16675661]

Details6. Voltage-dependent T-type calcium channel subunit alpha-1H

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Scaffold protein binding
Specific Function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name: CACNA1H
Uniprot ID: O95180
Uniprot Name: Voltage-dependent T-type calcium channel subunit alpha-1H
Molecular Weight: 259160.2 Da

References

Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [PubMed:1281221]
Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. doi: 10.1124/jpet.108.145672. Epub 2008 Oct 30. [PubMed:18974361]

Details7. Voltage-dependent calcium channel subunit alpha-2/delta-2

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Voltage-gated calcium channel activity
Specific Function: The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-t...
Gene Name: CACNA2D2
Uniprot ID: Q9NY47
Uniprot Name: Voltage-dependent calcium channel subunit alpha-2/delta-2
Molecular Weight: 129816.095 Da

References

Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [PubMed:1281221]
Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. doi: 10.1124/jpet.108.145672. Epub 2008 Oct 30. [PubMed:18974361]

Details8. Calmodulin

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Other

General Function: Titin binding
Specific Function: Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number...
Gene Name: CALM1
Uniprot ID: P0DP23
Uniprot Name: Calmodulin
Molecular Weight: 16837.47 Da

References

Bostrom SL, Westerlund C, Rochester S, Vogel HJ: Binding of a dihydropyridine felodipine-analogue to calmodulin and related calcium-binding proteins. Biochem Pharmacol. 1988 Oct 1;37(19):3723-8. [PubMed:3178884]
Johnson JD, Andrews CT, Khabbaza EJ, Mills JS: The interaction of felodipine with calcium-binding proteins. J Cardiovasc Pharmacol. 1987;10 Suppl 1:S53-9. [PubMed:2442519]
Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041]
Lamers JM, Verdouw PD, Mas-Oliva J: The effects of felodipine and bepridil on calcium-stimulated calmodulin binding and calcium pumping ATPase of cardiac sarcolemma before and after removal of endogenous calmodulin. Mol Cell Biochem. 1987 Dec;78(2):169-76. [PubMed:2964559]
Mills JS, Bailey BL, Johnson JD: Cooperativity among calmodulin's drug binding sites. Biochemistry. 1985 Aug 27;24(18):4897-902. [PubMed:4074665]
Walsh MP, Sutherland C, Scott-Woo GC: Effects of felodipine (a dihydropyridine calcium channel blocker) and analogues on calmodulin-dependent enzymes. Biochem Pharmacol. 1988 Apr 15;37(8):1569-80. [PubMed:2833901]

Details9. Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Metal ion binding
Specific Function: Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a preference for cGMP as...
Gene Name: PDE1B
Uniprot ID: Q01064
Uniprot Name: Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B
Molecular Weight: 61379.235 Da

References

Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041]
Sharma RK, Wang JH, Wu Z: Mechanisms of inhibition of calmodulin-stimulated cyclic nucleotide phosphodiesterase by dihydropyridine calcium antagonists. J Neurochem. 1997 Aug;69(2):845-50. [PubMed:9231746]

Details10. Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Metal ion binding
Specific Function: Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a higher affinity for cG...
Gene Name: PDE1A
Uniprot ID: P54750
Uniprot Name: Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A
Molecular Weight: 61251.38 Da

References

Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041]
Sharma RK, Wang JH, Wu Z: Mechanisms of inhibition of calmodulin-stimulated cyclic nucleotide phosphodiesterase by dihydropyridine calcium antagonists. J Neurochem. 1997 Aug;69(2):845-50. [PubMed:9231746]

Details11. Mineralocorticoid receptor

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Antagonist

General Function: Zinc ion binding
Specific Function: Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates targ...
Gene Name: NR3C2
Uniprot ID: P08235
Uniprot Name: Mineralocorticoid receptor
Molecular Weight: 107066.575 Da

References

Dietz JD, Du S, Bolten CW, Payne MA, Xia C, Blinn JR, Funder JW, Hu X: A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity. Hypertension. 2008 Mar;51(3):742-8. doi: 10.1161/HYPERTENSIONAHA.107.103580. Epub 2008 Feb 4. [PubMed:18250364]

Details12. Troponin C, skeletal muscle

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Other

General Function: Calcium ion binding
Specific Function: Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site fo...
Gene Name: TNNC2
Uniprot ID: P02585
Uniprot Name: Troponin C, skeletal muscle
Molecular Weight: 18121.895 Da

References

Bostrom SL, Westerlund C, Rochester S, Vogel HJ: Binding of a dihydropyridine felodipine-analogue to calmodulin and related calcium-binding proteins. Biochem Pharmacol. 1988 Oct 1;37(19):3723-8. [PubMed:3178884]
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Details13. Troponin C, slow skeletal and cardiac muscles

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Other

General Function: Troponin t binding
Specific Function: Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site fo...
Gene Name: TNNC1
Uniprot ID: P63316
Uniprot Name: Troponin C, slow skeletal and cardiac muscles
Molecular Weight: 18402.36 Da

References

Bostrom SL, Westerlund C, Rochester S, Vogel HJ: Binding of a dihydropyridine felodipine-analogue to calmodulin and related calcium-binding proteins. Biochem Pharmacol. 1988 Oct 1;37(19):3723-8. [PubMed:3178884]

Enzymes

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Galetin A, Clarke SE, Houston JB: Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Drug Metab Dispos. 2002 Dec;30(12):1512-22. [PubMed:12433827]
Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Details2. Cytochrome P450 3A5

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate

General Function: Oxygen binding
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP3A5
Uniprot ID: P20815
Uniprot Name: Cytochrome P450 3A5
Molecular Weight: 57108.065 Da

References

Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Details3. Cytochrome P450 3A7

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate

General Function: Oxygen binding
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP3A7
Uniprot ID: P24462
Uniprot Name: Cytochrome P450 3A7
Molecular Weight: 57525.03 Da

References

Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Details4. Cytochrome P450 2C8

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C8
Uniprot ID: P10632
Uniprot Name: Cytochrome P450 2C8
Molecular Weight: 55824.275 Da

References

Schoch GA, Yano JK, Sansen S, Dansette PM, Stout CD, Johnson EF: Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid. J Biol Chem. 2008 Jun 20;283(25):17227-37. doi: 10.1074/jbc.M802180200. Epub 2008 Apr 15. [PubMed:18413310]
Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807]
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Details5. Cytochrome P450 2C9

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C9
Uniprot ID: P11712
Uniprot Name: Cytochrome P450 2C9
Molecular Weight: 55627.365 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Ma B, Prueksaritanont T, Lin JH: Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30. [PubMed:10640508]

Details6. Cytochrome P450 2D6

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name: CYP2D6
Uniprot ID: P10635
Uniprot Name: Cytochrome P450 2D6
Molecular Weight: 55768.94 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Ma B, Prueksaritanont T, Lin JH: Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30. [PubMed:10640508]

Transporters

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	>60000	N/A	N/A	11716514
IC 50 (nM)	26300	N/A	N/A	11716514
IC 50 (nM)	32300	N/A	N/A	11716514

Details1. Multidrug resistance protein 1

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Xenobiotic-transporting atpase activity
Specific Function: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

References

Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [PubMed:11716514]

Details2. Bile salt export pump

Kind: Protein
Organism: Human
Pharmacological action: No
Actions: Substrate

General Function: Transporter activity
Specific Function: Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name: ABCB11
Uniprot ID: O95342
Uniprot Name: Bile salt export pump
Molecular Weight: 146405.83 Da

References

Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:33

Felodipine

Identification

Structure for Felodipine (DB01023)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

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References

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Enzymes

References

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Transporters

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References